Sarcoidosis is a multisystem granulomatous disorder of unknown etiology with protean systemic and ocular manifestations. Although intrathoracic manifestations are most common (90%), other organs frequently involved include the lymph nodes, skin, eyes, CNS, bones and joints, liver, and heart. Ocular involvement may be seen in up to 50% of patients with systemic disease, with uveitis being the most frequent manifestation. In most large series, sarcoidosis accounts for up to 10% of all cases of uveitis.
Sarcoidosis has a worldwide distribution, affecting all ethnic groups, with the highest prevalence seen in the northern European countries (40 cases per 100,000 people). In the United States the disease is up to 20 times more prevalent among African Americans than whites. Both sexes are affected, albeit with a slight female predominance; onset usually occurs usually between the ages of 20 and 50 years. Pediatric involvement is uncommon, and the clinical course is atypical. Children with early-onset sarcoidosis (younger than 5 years) are less likely than adults to manifest pulmonary disease and far more likely to have cutaneous and articular involvement; the disease course in older children (8–15 years) approximates that in adults.
The recently completed ACCESS (A Case Control Etiologic Study of Sarcoidosis) project suggests that specific occupations (in agricultural and pesticide-using industries) and workplace exposures (mold or mildew, musty odors, and insecticides) associated with microbe-rich environments may modestly increase the risk of developing sarcoidosis; however, no dominant factor could be identified. Similarly, molecular studies of tissue specimens of patients with sarcoidosis provide evidence that suggests that mycobacterial and, less convincingly, propionibacterial organisms may be important etiologic factors. A genetic predisposition for the development of the disease is suggested by the increased expression of class I and II HLA molecules, especially HLA-DRB1, in patients with biopsy-confirmed sarcoidosis. Familial clustering is observed, with siblings of patients having a fivefold increased risk of developing the disease. Patients with systemic sarcoidosis characteristically exhibit peripheral anergy on skin testing due to depression in delayed-type hypersensitivity, but at the target organ site, an active macrophage- and helper T lymphocyte (CD4+)–driven immunologic response is present, leading to granuloma formation.
The basic pathologic lesion of sarcoidosis is a noncaseating granuloma without histologic evidence of infection (Fig 6-51). The epithelioid cell is a polyhedral mononuclear histiocyte that is derived from monocytes of the peripheral blood or macrophages of the tissue. The tubercle of sarcoidosis is composed of the following:
multinucleate giant cells of the Langhans type, with nuclei at the periphery of the cell arranged in an arc or incomplete circle
a thin rim of lymphocytes
Central areas of the tubercle seldom undergo fibrinoid degeneration or, in skin lesions (lupus pernio), micronecrosis. Various types of inclusion bodies may occur in the cytoplasm of giant cells, including
or lamellar bodies: ovoid, basophilic, calcific bodies measuring up to 100 µm in diameter and also containing iron
asteroid bodies: star-shaped acidophilic bodies measuring up to 25 µm in diameter
Systemic sarcoidosis may present acutely, frequently with associated iridocyclitis in young patients, and spontaneously remit within 2 years of onset. One form of acute sarcoidosis is called Löfgren syndrome and consists of erythema nodosum, febrile arthropathy, bilateral hilar adenopathy, and acute iritis and is quite responsive to systemic corticosteroids; it has a good long-term prognosis. Another, termed Heerfordt syndrome (uveoparotid fever), is characterized by uveitis, parotitis, fever, and facial nerve palsy. Chronic sarcoidosis presents insidiously and is characterized by persistent disease of more than 2 years’ duration, frequently with interpulmonary involvement and chronic uveitis. Extended corticosteroid therapy may be required. Pulmonary disease is the major cause of morbidity; overall mortality from sarcoidosis approaches 5% but may be as high as 10% with neurosarcoidosis.
Sarcoidosis can affect any ocular tissue, including the orbit and adnexa. Cutaneous involvement is frequent, and orbital and eyelid granulomas are common (Fig 6-52). Palpebral and bulbar conjunctival nodules may also be observed and provide a readily accessible site for tissue biopsy (Fig 6-53). Lacrimal gland infiltration may cause keratoconjunctivitis sicca.
Anterior uveitis, presenting either acutely or as a chronic granulomatous iridocyclitis, is the most common ocular lesion, occurring in approximately two-thirds of patients with ocular sarcoidosis. Symptoms of uveal involvement are variable and frequently include mild to moderate blurring of vision and aching around the eyes. Typical biomicroscopic findings include
mutton-fat KPs (Fig 6-54), including those involving the anterior chamber angle
Koeppe and Busacca iris nodules (Fig 6-55)
white clumps of cells (“snowballs”) in the inferior anterior vitreous
Although the cornea is infrequently involved, nummular corneal infiltrates and inferior corneal endothelial opacification may be seen; band keratopathy may develop due to either chronic uveitis or hypercalcemia. Large iris granulomas, together with extensive posterior synechiae, may lead to iris bombé and angle-closure glaucoma. Peripheral anterior synechiae may also be extensive, encompassing the entire angle for 360° in advanced cases. Secondary glaucoma, together with sarcoid uveitis, may be severe and portends a poor prognosis with associated severe visual loss.
Posterior segment lesions occur in up to 20% of patients with ocular sarcoidosis. Vitreous infiltration is common and may be diffuse or appear more classically as yellowish white aggregates (snowballs), or linearly as a “string of pearls.” Nodular granulomas measuring ¼ to 1 disc diameter may be observed on the optic nerve, in both the retina and the choroid, either posteriorly or peripherally (Fig 6-56). Perivascular sheathing is also common, appearing most often as either a linear or segmental periphlebitis (Fig 6-57). Irregular nodular granulomas along venules have been termed candle-wax drippings, or taches de bougie. Occlusive retinal vascular disease, especially branch retinal vein occlusion and, less commonly, central retinal vein occlusion, together with peripheral retinal capillary nonperfusion, may lead to retinal neovascularization and vitreous hemorrhage. CME is frequently present, and optic disc edema without granulomatous invasion of the optic nerve may be observed in patients with papilledema and neurosarcoidosis.